Glucocorticoids

Overview

• Cortisol (hydrocortisone) and its synthetic derivatives 

• Mechanism 
  • ↓ the production of leukotrienes and prostaglandins  
    • inhibits phospholipase A₂
    • inhibits expression of COX-2
    • will also stimulate the bone marrow to produce neutrophils resulting in leukocytosis 
  • halts inflammatory cascade
    • ↓ leukocyte migration
    • ↓ capillary permeability
    • ↓ phagocytosis
    • ↓ platelet-activating factor
    • ↓ interleukins (e.g. IL-2)
  • may trigger apoptosis in dividing and non-dividing cells
    • used in cancer chemotherapy
• Clinical use
  • anti-inflammatory
  • immunosuppression
  • cancer chemotherapy (prednisone most common)
    • CLL
    • Hodgkin’s lymphomas
      • part of MOPP regimen
  • Addison disease
  • asthma
• Toxicity
  • must taper dose to avoid toxicity
  • suppression of ACTH → shock state if abrupt withdrawal
    • cortical atrophy
    • malaise
    • myalgia
    • arthralgia
    • fever
  • iatrogenic Cushing  syndrome
    • characteristics fat deposition
      • buffalo hump
      • moon facies
      • truncal obesity
    • muscle weakness and atrophy
    • thin skin, easy bruising
    • acne
  • osteoporosis 
    • vertebral fractures
    • aseptic hip necrosis
  • ↓ skeletal growth in children
  • hyperglycemia (diabetes)
    • due to ↑ gluconeogenesis
    • glaucoma, cataracts, and other complications can subsequently result
  • ↑ GI acid release
    • ulcers
  • Na+ retention
    • edema, HTN
    • hypokalemia alkalosis
    • hypocalcemia
  • ↓ wound healing 
  • ↑ infections
  • mental status changes
  • cataracts